Ambiguous Genitalia

also see Congenital Adrenal Hypoplasia

• Female differentiation is the default pathway
• Requirements for male differentiation:
  • Chromosomal level: TDF
  • H-P Level: GnRH, LH, FSH
  • Gonad level: MIF, Testosterone, DHT
  • External genitalia level: Response to androgens
• First 6-7 weeks, male and female same- then differentiate over next 6-7 weeks (“sensitive period”)

Clinical Findings In Infant That Raises Possibility of Intersexuality
Ambiguity: Classification
Female Pseudohermaphroditism
Male Pseudohermaphroditism (what is def of microphallus? answer below)
Androgen Insensitivity
5a-reductase deficiency
Syndromes
Gonadal Dysgenesis
Hermaphroditism

Ambiguity: Workup

• Electrolytes, serum glucose
• Karyotype
• Testosterone, DHT levels
• 'Pelvic/renal ultrasound'
• Steroid precursor profiles
• Urogenitography

Rules of Thumb

• Testes descend, ovaries don’t
• Testicular descent is directly linked to Mullerian duct regression
• Presence of uterus means no MIF action during the “sensitive” period of early gestation
• Testosterone, as well as MIF, functions as a locally-acting exocrine hormone in the development of the internal genital ducts
• External virilization, of any degree, is due to the effect of androgens
• The degree of external virilization proportionally predicts the degree of lower vaginal development
• With the exception of the phallus, circulating androgens masculinize the external genitalia only during a critical period (8-12 weeks)

from CHLA board review lecture 2005